Before the advent of cochlear prostheses, deafness-related changes following inner hair cell loss were of primarily academic interest. However, with the ability of cochlear prostheses to directly stimulate the auditory nerve, the condition of the remaining auditory system now has become of paramount importance. Results from Project I of the Program Project (Animal Psychophysics) indicate, for example, that the efficacy of cochlear implants is directly related to the amount of auditory nerve survival. The recent findings from our laboratory and others that cochlear prosthetic stimulation reduces deafness-related degeneration of auditory nerve and may prevent or reverse central auditory changes is therefore particularly exciting. These combined results have direct clinical relevance and suggest that early intervention with cochlear implants may be of great benefit in the treatment of deafness. Studies proposed in Project IV are to take the next steps in the analysis and understanding of deafness-related changes and their prevention or reversal by cochlear prosthetic stimulation. Specific Aim One is based on the hypothesis that auditory nerve degeneration occurs if it lacks electrical activity and replacement of this activity is the mechanism by which cochlear implants prevent the loss. It specifically questions whether a focal stimulation of just part of the cochlea is sufficient for the preventive effect. Specific Aim Two examines the influence of the length of period of deafness and age at onset of deafness on this prevention. Specific Aim Three is to determine if deafness-related auditory brain stem down-regulation can be reversed by cochlear prosthetic stimulation and the influence of the length of period of deafness on reversal. Specific Aim Four examines if chronic stimulation is required for full reversal. Specific Aim Five examines the influence of age at the onset of deafness on the reversal of auditory brain stem changes. These studies will use assessments ranging from ultrastructural to electrophysiological. Results will have important implications towards the treatment of deafness, the application of cochlear prostheses as well as towards a general understanding of cell death and neuronal plasticity.